Coccaro Emil F, Lee Royce J
Clinical Neuroscience Research Unit, Department of Psychiatry and Behavioral Neuroscience, Pritzker School of Medicine, The University of Chicago, Chicago, Illinois.
Hum Psychopharmacol. 2019 Nov;34(6):e2714. doi: 10.1002/hup.2714. Epub 2019 Nov 27.
Impulsive aggressive behavior is associated with reduced central function of serotonin (5-HT). Although selective serotonin reuptake inhibitors can reduce such behaviors, many with history of impulsive aggression do not respond adequately to selective serotonin reuptake inhibitors and may require treatment with a direct 5-HT agonist.
To test the hypothesis that pretreatment with the selective 5-HT2c agonist, lorcaserin, can reduce aggressive responding in impulsively aggressive individuals.
Ten male and female adults were given lorcaserin (20 mg), or a matching placebo, in random order, on 2 days separated by at least 1 week. The Taylor aggression paradigm was used to assess aggressive responding, which was represented by mean shock setting administered to an opponent and by frequency of setting high and extreme shock levels to the opponent.
Compared with placebo, lorcaserin attenuated provoked, but not unprovoked, aggression during the Taylor aggression paradigm. This was manifest by reduction in the frequency of selecting high and extreme levels of shock against the opponent.
Lorcaserin may possess anti-aggressive properties that could prove useful in the treatment of impulsive aggressive behavior in human subjects. These data, thus, provide a rationale for a follow-up randomized clinical trial of lorcaserin in individuals with prominent histories of impulsive aggressive behavior.
冲动攻击行为与血清素（5-羟色胺，5-HT）的中枢功能降低有关。尽管选择性血清素再摄取抑制剂可以减少此类行为，但许多有冲动攻击史的人对选择性血清素再摄取抑制剂反应不佳，可能需要用直接的5-HT激动剂进行治疗。
检验选择性5-HT2c激动剂洛卡塞林预处理可减少冲动攻击性个体的攻击反应这一假设。
10名成年男女被随机安排在至少间隔1周的2天里，分别服用洛卡塞林（20毫克）或匹配的安慰剂。采用泰勒攻击范式评估攻击反应，以对对手施加的平均电击强度以及对对手设置高电击强度和极高电击强度的频率来表示。
与安慰剂相比，在泰勒攻击范式中，洛卡塞林减轻了 provoked（此处provoked疑有误，可能是“受挑衅的”意思）攻击行为，但未减轻无端攻击行为。这表现为选择对对手施加高电击强度和极高电击强度的频率降低。
洛卡塞林可能具有抗攻击特性，这可能对治疗人类的冲动攻击行为有用。因此，这些数据为对有明显冲动攻击行为史的个体进行洛卡塞林后续随机临床试验提供了理论依据。
